|
|
Home
| Databases
| WorldLII
| Search
| Feedback
Precedent (Australian Lawyers Alliance) |
By Dr Chris Rudge and Professor Megan Munsie
Since the late 1990s, commentators have heralded stem cells as a revolution in medicine. A dominant narrative has been that stem cells will allow us to treat and cure various diseases by boosting the regenerative abilities of our own bodies, or by using our own tissues as a source of replacement cells to restore function to damaged organs. Such claims have engendered widespread hope among patients, as well as speculation in the healthcare community about the future of medicine.
During the last decade, stem cell tourism – in which patients, lured by the promise of hope, travel abroad to receive unregulated and often unfounded stem cell treatments – has become a familiar scenario. More recently, private Australian clinics offering purported stem cell treatments have proliferated. Though the science underpinning stem cell medicine still promises great innovations, significant technical obstacles need to be overcome to deliver on this promise. In this context, the premature adoption of unproven treatments poses grave dangers and risks to patients as well as to the fledgling biotechnology sector.
The Australian regulator of therapeutic goods, the Therapeutic Goods Administration (TGA), has recently responded to the growth of stem cell services and the risks they pose by updating its regulatory framework for biological products. In doing so, the TGA may be seen to have moved through three phases of regulation: from an effective absence (pre-2011), to structured regulation with broad exclusions for certain products (2011–2018), to the current third phase of more structured and controlled regulation. This article will provide a brief overview of stem cells and the different kinds of stem cell treatments available, before turning to the regulation of such treatments and exploring recent regulatory changes made by the federal government.
Stem cells are unique cells that can both make a copy of themselves (self-renew) and differentiate into other more specialised types of cells. Stem cells exist throughout life in most organs of the body. They are essential for normal growth and function and are often referred to as adult or tissue stem cells.[1] The best-known example of tissue stem cells are haematopoietic stem cells (HSCs), which are usually isolated from bone marrow or umbilical cord blood and can differentiate into all blood cell lineages. Mesenchymal stromal cells (MSCs) are isolated from a range of tissues (including adipose tissue, muscles, placenta, liver and kidney) and can differentiate into fat, cartilage and bone in laboratory studies.[2] These cells are also referred to as mesenchymal stem cells, although their biological potency and regenerative capacity is hotly debated in scientific circles.[3]
Through manipulation in the laboratory, scientists can also create more primitive stem cells that are capable of being coaxed to form any cell of the body; these are called pluripotent stem cells. These special cells can be isolated from donated assisted reproductive technology embryos (referred to as embryonic stem cells), or through genetic modification of a body cell to enforce a pluripotent state (so-called induced pluripotent stem cells or iPSCs). Pluripotent stem cells have attracted enormous interest as they can be theoretically used as an unlimited source of replacement cells, provided that they are appropriately coaxed.[4]
In Australia, the TGA regulates therapeutic goods through the Therapeutic Goods Act 1989 (Cth) (the Act). The TGA’s consumer guide notes that the only ‘proven safe and effective’ stem cell treatment in Australia is HSC transplantation for ‘the treatment disorders of the blood and immune system such as leukaemia’ – a procedure that has been used for decades in hospitals across Australia, and around the world, for certain disorders of the blood and immune system.[5] HSC transplants may be allogeneic or autologous. Allogeneic transplants involve a donor supplying cells to a patient for infusion; autologous transplants involve cells being harvested from and then later reinfused into the same patient.[6] Since HSC transplants for blood and immune diseases are ‘currently the only stem cell treatment modality with well-accepted clinical efficacy’,[7] and have additional regulatory oversight, they are exempt from the TGA’s regulation.[8]
Patients undergoing allogeneic HSC transplants undergo an ‘immunoablative’ regimen of chemotherapy to kill (ablate) pathological cells before they are infused with the donor cells.[9] The best donor for an allogeneic HSC transplant is a genetically identical (syngeneic) twin, or a sibling whose blood and tissues have been matched to the recipient. However, donor registries are now established worldwide to provide cells to recipients.[10] Although excluded from TGA regulation, allogeneic HSC transplants still carry risks. A significant proportion of patients’ illnesses relapse despite successful engraftment,[11] and HSC transplants are still regarded as ‘high-risk procedure[s]’ due to the toxicity of the pre-transplant preparative regimen and the risk of graft-versus-host disease (GVHD).[12]
Due to these risks, autologous HSC transplants have also become an established treatment for blood malignancies; the first successful cure of lymphoma was performed using autologous HSC transplants in 1978.[13]
Broadly, other clinical applications of HSCs, or the use of other types of stem cells, including the use of pluripotent stem cells, are yet to be fully evaluated. Such interventions should be considered experimental; only be administered as part of a clinical trial; and certainly not be commercially available. The TGA’s consumer guide warns that unproven stem cell treatments may lead to substantial financial costs, interrupt proven treatments, and/or disqualify the recipient from participation in registered clinical trials.[14] It also cautions that ‘unproven stem cell treatment may ... pose serious, potentially fatal, risks to your health including infection, allergic reactions, rejection of the cells by your immune system and the development of cancer’.[15] Despite these risks, many unproven and unapproved treatments involving stem cells have been administered in Australia in recent decades. The most common have been interventions marketed to consumers as ‘using your own stem cells to improve your health’.[16] By far the most commonly marketed stem cell intervention is the use of a patient’s own MSCs that are claimed to be isolated from fat, or less commonly bone marrow or blood.[17]
Adipose tissue is regarded as a ‘safe, easy and efficient source of MSCs for the purpose of autologous stem cell treatments’.[18] Initially thought to be capable of regenerating cartilage, bone, and other tissues in the body, current evidence suggests that MSCs can only differentiate in the laboratory,[19] and that if MSC infusions do afford a therapeutic effect it is by other means, such as by suppressing the immune system[20] or secreting factors that induce local repair.[21] However, the exact mechanisms and broad effects of these cells and treatments remains largely unknown and contested.[22] Comparatively few clinical trials have evaluated adipose-derived MSCs. Many interventions have been ‘rushed into clinical applications despite many questions about their safety, reproducibility, and standardization techniques’[23] and the alleged immunomodulatory effects of MSCs have been demonstrated only on cells grown in vitro and supported by xeno-contaminants (for example, bovine serum).[24]
A recent Australian study reported positive results in a randomised controlled trial investigating adipose-derived autologous stem cells for osteoarthritis. However, the study’s limitations – a small sample size, no blinding of participants, and exclusively patient-reported outcomes[25] – led several experts to criticise its methods.[26] In 2015, the TGA conducted a literature review of the safety of autologous MSC treatments and found sporadic reports of diverse adverse effects ranging from cyst formation, fat necrosis, to microthrombosis: dangers exacerbated by non-standardised expansion protocols.[27] The dangers of autologous MSC transplants are also illustrated by the 2013 death of a NSW woman who, after being administered adipose-derived MSCs for dementia, suffered hypovolemic shock caused by uncontrolled blood loss resulting from the clinician’s failure to discontinue the patient’s antiplatelet medication during the liposuction procedure.[28]
Allogeneic MSCs have generated excitement because the transplantation of uncultured MSCs does not appear to illicit an immune response, meaning that patients can have a universal donor and avoid immune-suppressive therapy.[29] This finding has led to MSCs being sold as ‘off-the-shelf’ products, with the first such products sold in Canada in 2012[30] and predictions of a future of ‘large-scale production and commercialization of cellular therapeutics by biopharmaceutical entities’.[31] The alleged ability of MSCs to supress GVHD responses has led clinicians to use MSCs to ‘support’ blood/immune disease-treating HSC transplants, with a single donor providing both HSCs and MSCs.[32] Nevertheless, it ‘has not yet been unequivocally proven’ that MSCs ‘home in’ on and repair damaged tissues in this procedure, as has been proposed,[33] and no trial has yet proven in ‘a clinically conclusive manner’ that MSCs can support autologous HSC transplants.[34]
The Act defines therapeutic goods broadly as any goods represented in any way to be for therapeutic use, including ingredients in, or containers for, therapeutic goods.[35] The definition encompasses prescription and non-prescription medicines, complementary medicines, medical devices and, since 2011, human tissue and cell-derived products (‘biologicals’), including stem cells. As noted above, the regulation of stem cell-based interventions in Australia has gone through three phases since stem cells first captured community attention.
Before 2011, human cell and tissue products (HCTPs) were either not regulated (that is, excluded from regulation), regulated as medicines or medical devices, or exempted from the Act. Following the discovery of embryonic stem cells in 1998, legislation was enacted in 2002 (both federally and later at state and territory levels[36]) to prohibit reproductive cloning, and to outlaw the use of assisted reproductive embryo-derived stem cells for research unless authorised by licence.[37] These restrictions on the use of human embryos remain today.
In the pre-2011 regime, excluded goods orders (EGOs) similar to those operative today excluded fresh viable human tissue, organs or bone marrow (other than blood) intended for direct donor-to-host transplantation from TGA regulation, thus permitting blood and immune-treating HSC transplants.[38] Similarly, banked tissues were exempted from regulation by pt 3-2 of the Act, and were not required to be registered on the Australian Register of Therapeutic Goods (ARTG).[39] Nevertheless, banked tissues were still regulated in that they had to comply with other parts of the Act relating to manufacturing principles. Non-excluded HCTPs were not regulated as ‘biologicals’ but as medicines or medical devices. However, as time went on, this regulatory approach was increasingly regarded as inadequate, as biological products were seen to have unique properties and pose unique risks, such as the risk of causing infectious diseases.[40] It was also recognised that not all biologicals pose the same level of risk and their potential for danger depends on the extent to which they are modified and how they are used in recipients.[41] Thus, in 2006, the Australian Health Ministers’ Conference proposed a separate regulatory framework for biologicals (the BRF) and endorsed four classes of biologicals (according to risk level). The BRF, however, was not implemented until 2011.
The BRF sought to regulate ‘biologicals’ as a distinct category of goods, and imposed a ‘comprehensive system of assessment and controls’ on biological products and suppliers at both the pre-market and post-market stages.[42] Implementation involved making several amendments to the Act, including a new definition of ‘biological’ encompassing all products made from or including HCTPs used for a specified therapeutic purpose, or any other product specified in the Act or regulations.[43] The BRF established a risk-based classification scheme for biologicals, requiring them to be registered on the ARTG in one of four classes. Class 1 biologicals are the lowest risk, involving homologous use and only minimal manipulation, while Class 4 biologicals are the highest risk. The use of cells derived from embryonic stem cells or genetically modified cells were classified at the highest level of risk. These classes were primarily defined by the extent to which a biological was ‘manipulated’ during manufacture (was it ‘minimally manipulated’ or ‘more than minimally manipulated’?) and the closeness of the biological’s intended use to its original function (was it for a ‘homologous’ use?). The scheme for ARTG registration of biologicals remains operative today, and ensures that biologicals are either included on the ARTG in Classes 1–4 or otherwise exempted or excluded under the Act or a relevant statutory instrument authorised by a relevant authority.[44]
In 2011, such relevant statutory instruments included a new EGO,[45] which was made under s7AA of the Act, and a determination declaring that certain products were not biologicals under the scheme (including HSCs used for haematopoietic reconstitution) but would be regulated as medicines.[46] The 2011 EGO maintained the pre-existing exclusion for donated organs, but was updated to specify that HSCs derived from bone marrow would be excluded.[47] It also excluded autologous stem cell treatments from regulation in certain circumstances: namely, where the cells were collected from a patient under the care of a registered medical practitioner and manufactured by that practitioner (or their supervisee) for treating a single indication in a single course of treatment by that practitioner (or supervisee).[48] This exclusion had significant implications: it allowed clinicians to ‘freely offer autologous stem cell based interventions’ and perform ‘unproven uses of autologous cells’ that were not ‘tested in clinical trials’ or subject to ‘stringent manufacturing standards’, leading to a proliferation of private stem cell clinics throughout Australia.[49]
In the years following the implementation of the BRF, scientific and legal scholars increasingly noted the proliferation of stem cell clinics, despite ‘a lack of scientific support for clinical applications and a lack of evidence of research participation, problematic inclusion and exclusion criteria, worrying uses of testimonials, unsupported claims, and the high cost of stem cell therapies’.[50] Critics of the new BRF claimed the EGO ignored the high level of risk associated with stem cell treatments, especially when cells were highly manipulated and used in a non-homologous manner, such as where adipose-derived MSCs were used to treat dementia.[51] Legal scholars described the BRF (and related instruments) as a ‘regulatory failure’ and questioned why there was no ‘evidence of a benefit to health or science attributed to the exemption’.[52] Moreover, scholars dismissed the efficacy of the so-called ‘soft law’ mechanisms – health practitioner professional guidelines and codes of conduct[53] – that might otherwise be thought to govern and restrict unproven treatments, identifying them as inadequate to protect against the risks and popularity of unproven stem cell treatments.[54]
Following two cycles of public consultation in 2015 and 2016, the TGA and federal government concluded in 2018 that changes to the BRF were necessary.[55] Relying on the extensive concerns raised in submissions, the TGA found that the BRF did not:
• align with international practice;
• account for new techniques involving significant cell manipulation (including extensive ex vivo culture methods for cell expansion);
• address new infection-prone cell injection techniques; and
• address the ubiquity of direct-to-consumer marketing of unproven treatments, which is inconsistent with health practitioner regulations on advertising.[56]
Although the BRF had provided a firm structure for the regulation and registration of biologicals through the ARTG, the scope of the exclusions and exemptions meant that the scheme was unjustifiably permissive.[57]
In response to the consultation process, several regulatory changes were made to restrict the availability of autologous HCTPs. In 2018, a new determination[58] replaced the 2011 EGO and specified new criteria for excluded goods; and in 2019, this determination was repealed and its changes incorporated into a new 2018 EGO.[59] This EGO maintains the original exclusions for donated organs and HSCs,[60] but now specifies that autologous HCTPs will be excluded only when manufactured by, or under the professional supervision of, a registered medical or dental practitioner in a hospital setting, and when they are collected from a patient in that hospital for use on that patient.[61] Further refinements introduced in 2019[62] specify that these excluded autologous HCTPs may be stored and tested outside the hospital setting, but only where the person testing or storing the product is under contract with the hospital.[63] Finally, the 2018 EGO introduces a significant new requirement that excluded goods must not be directly advertised to consumers.[64] These reforms ensure that proven products (such as skin and bone grafts) are still excluded from TGA regulation, but previous exclusions for unproven stem cell treatments are reined in by restricting their use to the hospital setting. Accordingly, the new exclusion criteria reflects the federal government’s view that hospital-related safety regulations external to the Act – such as hospital licensing and accreditation requirements – sufficiently mitigate the risks associated with certain autologous stem cell treatments.[65] As the TGA notes in respect of these excluded goods, ‘the Government has decided that there is appropriate external regulation for them’.[66]
In addition to these new exclusions, the 2018 reforms introduced changes to the Therapeutic Goods Regulations 1990 (Cth) (the Regulations) to exempt from regulation certain autologous HCTPs administered outside of hospitals. Schedule 5A of the Regulations exempts various autologous HCTPs from regulation by requiring products to be registered on the ARTG[67] and manufactured according to certain principles.[68] An exempt HCTP[69] must be collected from a patient under the clinical care of a registered medical or dental practitioner in the relevant state; it must be manufactured by, or under the supervision of, that same practitioner, and be used for a single indication and in a single procedure on the same patient; this use must also be a ‘homologous use’; and the HCTP must have undergone only ‘minimal manipulation’. These exemption conditions, two of which are examined below, are aimed at exempting only low-risk HCTPs from regulation, such as bone grafts for dental procedures or platelet-rich plasma injections for a single indication, such as osteoarthritis.[70]
The Regulations define ‘minimal manipulation’ as any process that does not alter the ‘biological characteristics, physiological functions or structural properties of the original cells or tissues that are relevant to the purpose for which the manufacturer of the goods intends the goods to be used’.[71] A 2019 TGA guidance document clarifies that centrifugation, trimming, washing, or freezing would constitute minimal manipulation, while cell culturing, in vitro differentiation or genetic modification would be more than minimal manipulation.[72] The guidance also indicates that MSCs derived from adipose tissue would be considered more than minimally manipulated as ‘the process applied to isolate the cells is likely to result in changes to their properties’.[73] Thus, autologous MSC transplants in which cells are isolated from adipose tissue are unlikely to qualify for exemption under the updated BRF. The Regulations also define ‘homologous use’ as the use of a product to ‘repair, reconstruct, replace or supplement the cells or tissues of a person ... if the goods will perform the same basic function or functions in the recipient as the original cells or tissues performed in the person from whom they were collected’.[74] Guidance documents further indicate that non-homologous use will occur when stromal vascular fraction – a complex cellular source of heterogenous cell populations, including MSCs – is ‘isolated from adipose tissue [and] used to treat musculoskeletal conditions, such as arthritis or tendonitis by regenerating or promoting the regeneration of articular cartilage or tendon’.[75] This is considered to be non-homologous use because ‘regenerating or promoting the regeneration of cartilage or tendon is not a basic function of the cells isolated from adipose tissue’.[76] In view of these new criteria, and their proposed interpretation by the TGA, many autologous stem cell treatments, such as adipose-derived MSC transplants for disorders including osteoarthritis, would not qualify for regulatory exemption.
Changes to the BRF since 2018 make it more difficult for Australian stem cell clinics to offer unproven treatments outside of a hospital setting. Such clinics must now limit or change their services so as to provide only exempted (for example, skin grafts or platelet rich plasma injections), excluded (hospital-based) or registered products to patients. If a private clinic believes their product is exempted, it must hold information on compliance with applicable standards, including evidence demonstrating the safety and efficacy of the product. The TGA may request and review this information if there is a safety issue and/or adverse event, and criminal penalties may be imposed for breaches under pt 3-2A of the Act.[77]
In efforts to avoid regulatory oversight, such clinics may attempt to contract with a hospital to manufacture stem cells that qualify for exclusion; however, this is unlikely to be feasible, as guidance documents on the 2018 EGO indicate that all manufacturing steps must occur in the hospital and that contractual parties must only store and test excluded goods, which must be administered in the hospital setting.[78] A stem cell clinic may also seek to register a biological on the ARTG in Class 1 or 2, which would involve submitting a comprehensive evidence dossier demonstrating the safety and efficacy of a product to obtain a manufacturing licence. However, while demonstrating safety and efficacy may be possible for large, research-intensive pharmaceutical companies, private clinics are unlikely to have the capacity to meet these evidence requirements.
Thus, although many aspects of these reforms are yet to be tested, the updated BRF takes positive steps towards restricting the use of unproven stem cell therapies in Australia. In the context of a number of longstanding ethical and public health concerns about the provision of unproven stem cell treatments, these regulatory reforms are a necessary step in providing greater protection for consumers. They also provide an incentive to fully develop an evidentiary basis for the development of future innovative stem cell medicines in Australia.
Dr Chris Rudge is research fellow at the University of Sydney Law School. His research focuses on medical regulation and the history of Australian medical law. He has published scholarly articles on the history of psychiatry and the use of controversial medical technologies. Chris recently completed a comprehensive report for the Medical Council of NSW on the Council’s power to discipline health practitioners under the Health Practitioner Regulation National Law Act 2009 (NSW). PHONE (02) 9351 0439 EMAIL christopher.rudge@sydney.edu.au.
Professor Megan Munsie is Deputy Director of the University of Melbourne’s Centre for Stem Cell Systems within the School of Biomedical Sciences. She has co-authored numerous educational resources for the public, health and educational professionals and contributed to the development of policy and regulation at a domestic and international level. In 2018 she was awarded the Public Service Award from the International Society for Stem Cell Research in recognition of her public outreach and policy advocacy in stem cell science. PHONE (03) 9035 8639 EMAIL megan.munsie@unimelb.edu.au.
[1] Although they exist in all postnatal organisms: see J Slack, Science of Stem Cells, Wiley, London, 2017, 2.
[2] R Ciccocioppo, A Cantore, D Chaimov et al, ‘Regenerative medicine: The red planet for clinicians’, International Emergency Medicine, Vol. 14(6), 2019, 915.
[3] D Sipp, PG Robey and L Turner, ‘Clear up this stem cell mess’, Nature, Vol. 561(7724), 2018, 455–7.
[4] A Trounson and ND DeWitt, ‘Pluripotent stem cells progressing to the clinic’, Nature Reviews Molecular Cell Biology, Vol. 17(3), 2016, 194–200.
[5] Therapeutic Goods Administration (TGA), Stem Cell Treatments and Regulation – A Quick Guide for Consumers (27 July 2018) <https://www.tga.gov.au/community-qa/stem-cell-treatments-and-regulation-quick-guide-consumers>.
[6] W Vaughan, ‘The principles and overview of autologous hematopoietic stem cell transplantation’ in M Bishop (ed), Hematopoietic Stem Cell Transplantation, Springer, 2009, 23.
[7] S Unal and D Uckan-Cetınkaya, ‘Hematopoietic stem cell transplantation in pediatric diseases’ in N El-Badri (ed), Advances in Stem Cell Therapy: Bench to Bedside, Humana Press, 2017, 3.
[8] TGA, above note 5.
[9] Ibid.
[10] JM Goldman, ‘Allogeneic stem cell transplantation: The last century’ in HM Lazarus and MJ Laughlin (eds), Allogeneic Stem Cell Transplantation, Contemporary Hematology, Humana Press, 2010, 3.
[11] C Chabannon et al, ‘Cell therapy in hematology: HSC transplantation in 2012’ in J-F Stoltz (ed), Regenerative Medicine and Cell Therapy, IOS Press, 2012, 154.
[12] See P Hematti, ‘Mesenchymal stromal/stem cell transplantation: From tissue regeneration to immune modulation’ in S Sell (ed), Stem Cells Handbook, Humana Press, 2013, 392; HM Lazarus and MJ Laughlin, ‘Preface’ in HM Lazarus and MJ Laughlin (eds), Allogeneic Stem Cell Transplantation, Contemporary Hematology, Humana Press, 2010, vii.
[13] O Lahoud, C Sauter, P Hamlin et al, ‘High-dose chemotherapy and autologous stem cell transplant in older patients with lymphoma’, Current Oncology Reports, Vol. 17(9), 2015, 42.
[14] Ibid.
[15] TGA, above note 5.
[16] M Munsie, T Lysaght, T Hendl et al, ‘Open for business: A comparative study of websites selling autologous stem cells in Australia and Japan’, Regenerative Medicine, Vol. 12(7), 2017, 777–90.
[17] Ibid.
[18] A El-Badawy, S Ahmed and N El-Badri, ‘Adipose-derived stem cell-based therapies in regenerative medicine’, in N El-Badri, above note 7, 117.
[19] M Dominici, K Le Blanc, I Mueller et al, ‘Minimal criteria for defining multipotent mesenchymal stromal cells: The International Society for Cellular Therapy position statement’, Cytotherapy, Vol. 8, 2006, 315–7.
[20] A Galleu, Y Riffo-Vasquez, C Trento et al, ‘Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated mmunomodulation,’ Science Translational Medicine, Vol. 15(9), 2017, 416; GM Spaggiari, A Capobianco, H Abdelrazik et al, ‘Mesenchymal stem cells inhibit natural killer‐cell proliferation, cytotoxicity, and cytokine production: Role of Indoleamine 2,3‐Dioxygenase and Prostaglandin E2’, Blood, Vol. 111(3), 2008, 1327–33.
[21] Hematti, above note 12, 395.
[22] Sipp, Robey and Turner, above note 3.
[23] A El-Badawy, S Ahmed and N El-Badri, ‘Adipose-derived stem cell-based therapies in regenerative medicine’, in El-Badri, above note 7, 131.
[24] Ibid.
[25] J Frietag, D Bates, J Wickham et al, ‘Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: A randomized controlled trial’, Regenerative Medicine (Epub ahead of print), <https://www.futuremedicine.com/doi/pdf/10.2217/rme-2018-0161>.
[26] Media Watch (ABC), ‘Stem Cell “Miracle”’, 3 June 2019, <https://www.abc.net.au/mediawatch/episodes/stem-cell/11172810>.
[27] TGA, Regulation of Autologous Stem Cell Therapies (Discussion Paper) January 2015, attachment 2, 30, <https://www.tga.gov.au/sites/default/files/consult-autologous-stem-cell-150106.pdf>.
[28] T Lysaght, W Lipworth, T Hendl et al, ‘The deadly business of an unregulated global stem cell industry’, Journal of Medical Ethics, Vol. 43, 2017, 744–6.
[29] M Sundin M, O Ringdén, B Sundberg, ‘No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients’ Haematologica, Vol. 92, 2007, 1208–15; N Bich Vu, ‘Off-the-shelf mesenchymal stem cell technology,’ in P Van Pham (ed), Stem Cell Drugs: A New Generation of Biopharmaceuticals, Springer, 2018, 123.
[30] P Rameshwar, CA Moore, NN Shah et al, ‘An update on the therapeutic potential of somatic stem cells’, Methods in Molecular Biology, Vol. 1842, 2018, 10–11.
[31] Hematti, above note 12, 393.
[32] See M Battiwalla and P Hematti, ‘Mesenchymal stem cells in hematopoietic stem cell transplantation’ Cytotherapy, Vol. 11(5), 2009, 503–15.
[33] LA Solchaga and HM Lazarus, ‘Therapeutic potential of mesenchymal stem cells in hematopoietic stem cell transplantation’ in Allogeneic Stem Cell Transplantation, Contemporary Hematology (Humana Press 2010), 486; J Barminko, A Gray, T Maguire et al, ‘Mesenchymal stromal cell mechanisms of immunomodulation and homing’ in L Chase and M Vemuri (eds), Mesenchymal Cell Therapy, Springer, 2013, 15–38.
[34] Hematti, above note 12, 392.
[35] Therapeutic Goods Act 1989 (Cth) (Act), s3.
[36] Through a co-operative scheme as per a COAG agreement: see COAG, Research Involving Human Embryos and Prohibition of Human Cloning (2004) <https://www.coag.gov.au/about-coag/agreements/research-involving-human-embryos-and-prohibition-human-cloning>; also see Prohibition of Cloning Act 2002 (Cth) and Research Involving Human Embryos Act 2002 (Cth); in NSW, see Human Cloning for Reproduction and Other Prohibited Practices Act 2003 (NSW) and Research Involving Human Embryos (New South Wales) Act 2003 (NSW).
[37] From the Embryo Research Licensing Committee of the National Health and Medical Research Council (NHMRC). See SN Then, ‘Regulation of human stem cell research in Australia’, Stem Cell Reports and Review, Vol. 5(1), 2009, 1–5.
[38] See Therapeutic Goods (Excluded Goods) Order No. 1 of 1998, item 3(o); and Therapeutic Goods (Excluded Goods) Order No. 1 of 1997.
[39] In relation to exempt goods, see Act, pt 3-2 div 1 ss18(1) and 32CA(2). Banked tissues were still regulated in that they had to comply with other parts of the Act relating to manufacturing principles: see TGA, Australian Regulatory Guidelines for Biologicals: Part 1 – Introduction to the Australian Regulatory Guidelines for Biologicals (June 2011) 18, <https://www.abc.net.au/cm/lb/4058676/data/australian-regulatory-guidelines-for-biologicals-data.pdf>; the Act, pt 3-2.
[40] See Orders, above note 38.
[41] Ibid.
[42] Ibid, 14.
[43] Act, s32A.
[44] Ibid.
[45] Therapeutic Goods (Excluded Goods) Order No. 1 of 2011 (in force 30 May 2011); it replaced the Therapeutic Goods (Excluded Goods) Order No. 1 of 2008.
[46] See Therapeutic Goods (Things that are not Biologicals) Determination No. 1 of 2011. Medicines are still subject to manufacturing principles and guidelines provided, before 2018, in the Therapeutic Goods (Manufacturing Principles) Determination 2013 and, after 2018, in the Therapeutic Goods (Manufacturing Principles) Determination 2018.
[47] Therapeutic Goods (Excluded Goods) Order No. 1 of 2011, items 4(o) and 4(p).
[48] See Therapeutic Goods (Excluded Goods) Order No. 1 of 2011, item 4(q).
[49] Munsie, Lysaght, Hendl et al, above note 16.
[50] A McLean, C Stewart and Ian Kerridge, ‘The emergence and popularisation of autologous somatic cellular therapies in Australia: Therapeutic innovation or regulatory failure?’ Journal of Law and Medicine, Vol. 22, 2014, 71–4.
[51] B Tigerstrom, ‘New regulatory pathways for stem cell-based therapies: Comparison and critique of potential models’ in P Van Pham and A Roseman (eds), Stem Cells in Clinical Applications: Safety, Ethics and Regulations, Springer, 2017, 173–99.
[52] Ibid.
[53] These forms of soft law include the Medical Board of Australia’s Good Medical Practice: Code of Conduct; the Australian Health Practitioner Regulation Agency’s Guidelines for Advertising Regulated Health Services (May 2014) <https://www.ahpra.gov.au/Publications/Advertising-resources/Legislation-guidelines/Advertising-guidelines.aspx>; and the Guidelines for Stem Cell Research and Clinical Translation published by the International Society for Stem Cell Research (May 2016) <https://www.isscr.org/docs/default-source/all-isscr-guidelines/guidelines-2016/isscr-guidelines-for-stem-cell-research-and-clinical-translationd67119731dff6ddbb37cff0000940c19.pdf?sfvrsn=4>.
[54] See P Foong, ‘Stemming the tide of unproven autologous stem cell therapies in Australia’, UNSW Law Journal Forum, Vol. 3, 2018, 6.
[55] See TGA, above note 5; TGA, Consultation: Regulation of autologous cell and tissue products and proposed consequential changes to the classification of biologicals (Discussion Paper, August 2016) <https://www.tga.gov.au/sites/default/files/consultation-regulation-autologous-cell-and-tissue-products.pdf>.
[56] For instance, the Health Practitioner National Law 2009 (NSW), s133(d) prohibits health practitioners advertising a regulated health service that ‘creates an unreasonable expectation of beneficial treatment’.
[57] TGA, above note 55, 8–9.
[58] Therapeutic Goods (Human Cells, Tissues and Organs) Determination 2018 (Cth).
[59] This Determination was amended by an amendment Determination, the Therapeutic Goods Amendment (Excluded Goods) Determination 2019 (Cth).
[60] Therapeutic Goods (Human Cells, Tissues and Organs) Determination 2018 (Cth), items 4(b)–(d); and Therapeutic Goods (Excluded Goods) Determination 2018, items 4B–4D.
[61] Therapeutic Goods (Human Cells, Tissues and Organs) Determination 2018 (Cth), item 4(a)(ii); and Therapeutic Goods (Excluded Goods) Determination 2018, items 4A(a)–(b), 4A(d)(a).
[62] See Therapeutic Goods Amendment (Excluded Goods) Determination 2019 (Cth); Therapeutic Goods (Excluded Goods) Determination 2018, item 4A(d).
[63] Therapeutic Goods (Excluded Goods) Determination 2018, item 4A(d).
[64] Therapeutic Goods (Human Cells, Tissues and Organs) Determination 2018 (Cth), item 4(iv); Therapeutic Goods (Excluded Goods) Determination 2018, item 4A(d)(b).
[65] See I Prosser and J Mason, ‘Changes to the Regulation of Autologous Cells and Tissues’ (2018) Therapeutic Goods Administration, <https://www.tga.gov.au/tga-presentation-changes-regulation-autologous-human-cells-and-tissue-products>, slide 10.
[66] TGA, What is regulated as a biological? (September 2019) <https://www.tga.gov.au/sites/default/files/what-regulated-biological.pdf>.
[67] See Act, pts 3-2 (Registering and listing of therapeutic goods) and 3-2A (Biologicals).
[68] See Act, pt 3-3 (Manufacturing of therapeutic goods).
[69] The relevant regulatory item for stem cell treatments (biologicals) is in sch 5A, item 13, which sets out the criteria that a given HCTP must meet to qualify for exemption.
[70] TGA, Biologicals regulatory framework proposed changes to start on 1 July 2018 (April 2018) 13–14, <https://www.tga.gov.au/sites/default/files/biologicals-regulatory-framework-proposed-changes-start-1-july-2018.pdf>.
[71] Regulations, reg 3B(3).
[72] TGA, Method of preparation: Interpretation of minimal manipulation (July, 2019) <https://www.tga.gov.au/method-preparation-interpretation-minimal-manipulation>.
[73] Ibid, 5.
[74] Regulations, reg 3B(4).
[75] TGA, Intended use: Interpretation of homologous use (July 2018) <https://www.tga.gov.au/sites/default/files/intended-use-interpretation-homologous-use.pdf>, 5.
[76] Ibid.
[77] See Act, ss30EA, 30EB, 30EC, 30ECA.
[78] TGA, Excluded autologous human cells and tissues (September 2019) <https://www.tga.gov.au/sites/default/files/excluded-autologous-human-cells-and-tissues.pdf>.
AustLII:
Copyright Policy
|
Disclaimers
|
Privacy Policy
|
Feedback
URL: http://www.austlii.edu.au/au/journals/PrecedentAULA/2020/7.html